Goodfellow R M, Williams A S, Levin J L, Williams B D, Morgan B P
Department of Rheumatology, University of Wales College of Medicine, Cardiff, UK.
Clin Exp Immunol. 1997 Oct;110(1):45-52. doi: 10.1046/j.1365-2249.1997.5111408.x.
Complement activation has been implicated in the pathogenesis of human rheumatoid arthritis. We sought to determine whether inhibition of complement (C) using sCR1 could influence the development and progression of antigen arthritis in the rat, a recognized model of human chronic synovitis. The effect of C inhibition, systemically and locally, on three different stages of disease was examined: (i) prophylaxis, (ii) treatment of established inflammation, and (iii) prevention of antigen-induced flares of disease. Arthritis was assessed by knee swelling and by histological examination. Our results show that intra-articular injection of sCR1 prior to disease onset reduced joint swelling and development of arthritis, whereas systemic administration was ineffective. Treatment of established arthritis with intraarticular sCR1 3 days after disease onset caused a transient reduction in swelling, but treatment 7 days after disease onset had no effect on disease. An intra-articular dose of sCR1 given at the time of disease flares had a small, yet significant effect on knee swelling. We conclude that complement activation is important in the initiation and maintenance of inflammation in antigen arthritis. The potent effect of local C inhibition suggests that C biosynthesis and activation within the joint contributes to inflammation in this model of arthritis.
补体激活已被认为与人类类风湿性关节炎的发病机制有关。我们试图确定使用可溶性补体受体1（sCR1）抑制补体是否会影响大鼠抗原性关节炎的发生和发展，大鼠抗原性关节炎是一种公认的人类慢性滑膜炎模型。我们研究了全身和局部抑制补体对疾病三个不同阶段的影响：（i）预防，（ii）对已确立炎症的治疗，以及（iii）预防抗原诱导的疾病复发。通过膝关节肿胀和组织学检查评估关节炎情况。我们的结果表明，在疾病发作前关节内注射sCR1可减轻关节肿胀和关节炎的发展，而全身给药则无效。在疾病发作后3天用关节内注射sCR1治疗已确立的关节炎可使肿胀暂时减轻，但在疾病发作后7天治疗对疾病没有影响。在疾病复发时给予关节内剂量的sCR1对膝关节肿胀有微小但显著的影响。我们得出结论，补体激活在抗原性关节炎炎症的启动和维持中起重要作用。局部补体抑制的显著效果表明，关节内补体的生物合成和激活在该关节炎模型中促成了炎症反应。
